Methods of identifying individuals at risk for coronary artery disease (CAD) mortality, primarily due to platelet mediated cardiovascular events such as myocardial infarction (MI), are a priority for reducing the burden of cardiovascular disease. To identify novel risk factors, genome-wide surveys of allelic variation, structural variation, and gene expression can identify loci associated with CAD, though not all are subsequently associated with cardiovascular events.
Aspirin is a potent inhibitor of COX-1 and an inhibitor of platelet function. Aspirin is one of the most commonly prescribed medications for the prevention of cardiovascular events, suggesting that aspirin interacts with biological pathways that may underlie these events. Platelet function assays can be used as surrogates for the effects of aspirin and demonstrate variability, reproducibility, and heritability, despite complete suppression of platelet COX-1. However, platelet function testing is not widely available primarily due to technical complexity, such as the need for specialized equipment and trained personnel. For example, point-of-care tests require testing to be completed within hours of phlebotomy and thus are out of reach for the vast majority of outpatients on aspirin. Further, most patients taking aspirin for chronic prevention are outpatients where results at the point-of-care are not required. Instead, testing in central laboratories would be sufficient for determining aspirin response in the outpatient setting.
It would be beneficial if aspirin could be used as a probe in conjunction with whole blood gene expression profiling to elucidate novel biological pathways associated with platelet function in response to aspirin and cardiovascular outcomes.